Activity-based projection mapping to identify cortical representations of internal states

Brian Hsueh

(Stanford University)

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Date: January 14, 2018


How cortical ensembles encode internal homeostatic states and coordinate with other structures throughout the brain to drive adaptive behavior remains a fundamental question in neurobiology. To achieve access to such cortical populations, we developed an expanded viral toolkit for permanent genetic labeling of activity-defined neuronal populations both for unbiased, whole-brain labeling, and for targeted, projection-specific labeling. In conjunction with a computational framework enabling automated quantification of cortical projections in atlas-registered, cleared whole mouse brains, we performed a brain-wide screen for projections activated by hunger, and found increased activation of a projection from posterior insular cortex to the amygdala. Optogenetic stimulation of this projection was sufficient to increase food consumption in otherwise sated animals without affecting water consumption, and elicit aversion of a neutral environment, while optogenetic inhibition suppressed consumption in fasted animals. These findings demonstrate the utility of this new viral approach for activity-dependent input mapping, and support the role of posterior insula in top-down coordination of responses to perturbed homeostatic states.

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Related papers

[1] Hsueh B, Burns VM, Pauerstein P, Holzem K, Ye L, Engberg K, Wang AC, Gu X, Chakravarthy H, Arda HE, Charville G, Vogel H, Efimov IR, Kim S, Deisseroth K. (2017). Pathways to clinical CLARITY: volumetric analysis of irregular, soft, and heterogeneous tissues in development and disease. Scientific Reports. 7(1):5899. doi: 10.1038/s41598-017-05614-4.

Created: Thursday, January 17th, 2019